BACKGROUND: The benefit from intervention in elderly patients with symptomatic severe aortic stenosis (AS) and high comorbidity is unknown. Our aims were to establish the correlation between the Charlson comorbidity index and the prognosis of octogenarians with symptomatic sever AS and to identify patients who might not benefit from intervention. METHODS: We used the data from PEGASO (Pronóstico de la Estenosis Grave Aórtica Sintomática del Octogenario--Prognosis of symptomatic severe aortic stenosis in octogenarians), a prospective registry that included consecutively 928 patients aged ≥ 80 years with severe symptomatic AS. RESULTS: The mean Charlson comorbidity index was 3.0 ± 1.7, a total of 151 patients (16.3%) presented high comorbidity (index ≥ 5). Median survival was lower for patients with high comorbidity than for those without (16.7 ± 1.2 vs. 26.5 ± 0.6 months, p 0.10). In multivariate analysis, the only variables that were independently associated with prognosis were planned medical management and Charlson index. Patients with high comorbidity presented non-cardiac death more frequently than those who had not (28.6% vs. 19.5%, p = 0.008). CONCLUSIONS: One sixth of octogenarians with symptomatic severe AS have very high comorbidity (Charlson index ≥ 5). These patients have a poor prognosis in the short term and do not seem to benefit from interventional treatment.